Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation

Abstract

Background/aims-Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The eYciency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. Methods-33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by KaplanMeier survival curves. Results-Of the 33 tumours analysed, 16showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The diVerence in survival between the two groups was highly significant (p<0.0001). Conclusion-The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and eYcient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy

“…Starting a little over a decade ago, investigators around the world began to report that chromosomal and transcriptional features of primary uveal melanoma cells were strongly associated with the pa tient's likelihood of developing subsequent extraophthalmic metastasis and metastatic death (25,(29)(30)(31)(32)(33)(34)(35) Several authors have shown that these chromosomal and transcriptional features can be determined on tumor specimens obtained by FNAB changing the indication for FNAB from purely diagnostic to investigational-prognostic (24,25,(36)(37)(38) . During the past few years, investigators from several of these centers have reported their experience with cytogenetic testing of the obtained FNAB aspirates (25,27,35,37,(39)(40)(41) .…”

What is the significance of vortex vein invasion in uveal melanoma?

“…Less signals for chromosome 3 in relation to chromosome 8 were considered to represent genetic imbalance (GI), a term encompassing various combinations of either loss or retention of chromosome 3, in relation to no change or gains of 8q. 17 This study is descriptive in nature. The number of cases studies was judged to be small for a formal statistical assessment.…”

“…FISH analysis was performed according to standard protocols recommended by the manufacturers. 17 For each case the numbers of signal per cell for chromosomes 3 and 8 were counted, and a total of 300 cells scored. Less signals for chromosome 3 in relation to chromosome 8 were considered to represent genetic imbalance (GI), a term encompassing various combinations of either loss or retention of chromosome 3, in relation to no change or gains of 8q.…”

“…Prospective analysis was performed on newly prepared chromosome preparations, from both cultured and direct samples, made using well-established standard techniques. 17 Chromosomes 3 and 8 a-satellite probes (labelled red and green, respectively) were used and supplied by Vysis. FISH analysis was performed according to standard protocols recommended by the manufacturers.…”

“…17 FISH data were available for 28 of 29 (96.6%) of uveal melanomas with vortex vein invasion. Of these, 25 of 29 (86.2%) showed GI.…”